Chemistry Reference
In-Depth Information
sequence selectivity has been demonstrated in many cases.
6
However, short peptides
lack the DNA-binding affi nity of the native proteins. This is why dimeric peptides
have been used for such studies, instead.
7
Peptides can become powerful tools in our hands if a specifi c protein - DNA
recognition code is determined. There is a big debate between different research
groups as to whether a 'DNA recognition code' exists.
8
As many structures of
DNA-transcription factor complexes became known in atomic detail, it was recog-
nized that some DNA-binding proteins share the same structural framework, such
as helix - turn - helix, zinc fi nger and the basic domain leucine zipper motifs. Suzuki
et al
.
8
demonstrated that a simple code for DNA recognition can be applied in the
case of transcription factors. According to Suzuki
et al.
,
8
the major part of the DNA
recognition code consists of two types of rules; chemical and stereochemical. The
chemical rules are based on the intrinsic chemical ability of a given residue and a
base to form chemical contacts, either a hydrogen bond or hydrophobic interaction
in the major groove. The chemical rules making up the DNA recognition code are
given in Table 12.1 .
In addition, the main target for hydrophobic interaction in the major groove
of DNA is the single methyl group of the T base, being recognized by hydrophobic
residues such as Ala, Val, Ile, Leu, Met, Phe, Tyr, Trp and Thr. Stereochemical rules
are summarized in a stereochemical chart which is deduced from crystal and NMR
structures of DNA-protein complexes.
8
This stereochemical chart indicates which
Table 12.1
Single amino acid-single base contacts (chemical rules). The 'specifi c' residue
partners are shown in bold, while nonspecifi c partners are in plain text. Chemical merit points,
semi-arbitrary numbers associated with particular contacts, are used to quantify the energy
and specifi city of a pairing between an amino acid residue and a nucleotide base. For
example, the interaction of Arg (to G), which is particularly favourable and specifi c, with the
residue receives 15 merit points, while the interaction between Ser (to any base), which is
less specifi c, is given 10 points. (M. Suzuki, N. Yagi, DNA-recognition code of transcription
factors in the helix-turn-helix,probe helix,hormone receptor, and zinc fi nger families.
Proc.
Natl. Acad. Sci
, 91, 12357-12361. Copyright 1994, National Academy of Sciences, USA.)
small
medium
large
aromatic
A
Cys, Ser, Thr
10
Asn
15
Gln
15
Tyr
5
Asp
9
Glu
9
Trp
5
His
8
Arg, Lys
3
Met
5
T
Ala
10
Val, Ile
12
Leu, Met
12
Tyr, Phe
12
Cys,Ser, Thr
Asn
10
Gln
10
Trp
12
His
8
Arg, Lys
5
G
Cys, Ser, Thr
10
His
12
Arg, Lys
15
Ty r
5
Asn
10
Gln
10
C
Val
8
Asp
12
Glu
12
Tyr, Phe
8
Cys, Ser, Thr
10
Asn
10
Gln
10
Trp
8
His
8
Leu, Met
8
Ile
8
